Year Of Treatment In Patients Research Articles

Experiencia tras el cambio de insulina glargina U100 a glargina U300 en pacientes con diabetes tipo 1. Estudio tras un año de tratamiento en vida real

IntroductionCurrent treatment of type 1 diabetes mellitus (T1DM) does not always achieve metabolic control because, among other things, the ocurrence of hypoglycemic events associated to insulin use. Material and methodsA descriptive real life study of 247 T1DM patients, 55.5% male, aged 46.53 ± 16.23 years, and with a mean diabetes duration of 21.89 ± 11.99 years, who were switched from basal insulin glargine U100 to glargine U300. The primary endpoints were changes in Hba1c and number of hypoglycemic events, while secondary endpoints included changes in weight and insulin dose after 6 and 12 months. ResultsAfter one year, no changes were seen in HbA1c, but the proportion of patients with HbA1c values <7.5% increased at 6 months (33.5 vs. 40.5%; P<0.05) and remained stable during one year of follow-up. Hypoglycemic events significantly decreased after one year of treatment in patients with previous hypoglycemic events. No changes were seen in body weight.Total insulin dose (U/kg) increased 7.24% at 6 months of treatment and by 8.69% at one year, mainly due to basal insulin. No changes were seen between the doses given at 6 and 12 months. These changes were similar in the different metabolic control groups and in patients with or without hypoglycemia. This increase was not related with prior basal insulin dose, baseline HbA1c level, number of hypoglycemic events or baseline weight. DiscussionGlargine U300 is a good basal insulin alternative to treat T1DM, improving metabolic control in patients with HbA1c levels >7,5 and decreasing hypoglycemic events in patients with history of hypoglycemia without increasing body weight.

Predicting prognosis in patients with first-episode psychosis using auditory P300: A 1-year follow-up study

ObjectiveTo clarify the role of auditory P300 in predicting prognosis in patients with first-episode psychosis (FEP) during a 1-year follow-up. MethodsAuditory P300 of 24 patients with FEP and 24 matched healthy control (HC) participants were measured at baseline. The clinical status of the FEP patients was assessed at baseline and reassessed after 1 year. P300 amplitudes and latencies among the groups were analyzed using repeated measures analysis of variance. Multiple regression analysis was conducted to assess the predictive value of P300 in patients with FEP during the 1-year follow-up. ResultsAuditory P300 amplitudes were significantly smaller in FEP patients than HCs. Higher baseline P300 amplitudes at CPz significantly predicted better improvements in the Positive and Negative Syndrome Scale total, positive, and general scores, as well as in the Global Assessment of Functioning and Brief Psychiatric Rating Scale. ConclusionsP300 may predict improvements in symptoms, functional status, and overall psychiatric status in patients with FEP. SignificanceWe first show that P300 amplitude at baseline predicts symptomatic and functional improvements after 1 year of treatment in patients with FEP. This finding may aid in effective interventions from the beginning of a psychotic episode to improve subsequent outcomes in clinical practice.

The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors.

To investigate the effect of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with adalimumab or infliximab on maintaining serum drug and clinical outcomes after the first year of treatment in patients with rheumatoid arthritis (RA). Second, to assess the influence of methotrexate (MTX) dose on these outcomes. Ninety-two patients with RA starting infliximab (n = 67) or adalimumab (n = 25) tumor necrosis factor inhibitor (TNFi) with available drug levels and clinical improvement assessment (European League Against Rheumatism [EULAR] response) after 12months were included. Patients were grouped according to concomitant csDMARD use: (i) TNFi monotherapy; (ii) TNFi+MTX; (iii) TNFi with csDMARDs other than MTX (TNFi+OD). Patients receiving MTX were also classified by dose as < 15mg/week (TNFi+MTX<15) and ≥ 15mg/week (TNFi+MTX≥15). Logistic regression analyses were employed. More TNFi+MTX patients had circulating serum TNFi at 12months (71% TNFi+MTX vs. 20% TNFi+OD vs. 9% TNFi monotherapy). Of these, the probability of maintaining serum TNFi levels was twice (OR 2.3; p = 0.06) than that of patients without MTX. However, statistically significant results were observed only for the highest MTX dose (OR 4.9; p = 0.02). Most patients achieving good EULAR response were treated with TNFi+MTX (81%). The probability of achieving this response was three times higher in patients within the TNFi+MTX group (OR 3.4; p = 0.03); however, no differences were found with regard to MTX dose. The persistence of serum TNFi and the probability of achieving clinical response are influenced by MTX but not by OD in patients with RA treated with infliximab or adalimumab.

Long-term Reduction in Brain MRI Disease Activity and Atrophy after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Long-term Reduction in Brain MRI Disease Activity and Atrophy after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Long-term Reduction of Relapse Rate and Confirmed Disability progression after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Long-term Reduction of Relapse Rate and Confirmed Disability progression after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B

Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB). A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded. A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001). Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients. We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events.

Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan.

We determined the antiviral potency and viral breakthrough rate after 10years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection. The cumulative rates of undetectable hepatitis B virus DNA (HBV-DNA, < 2.1logcopies/mL), alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroclearance, hepatitis B surface antigen (HBsAg) seroclearance, and viral breakthrough of 1094 nucleos(t)ide analogue-naïve CHB patients (HBeAg-positive: 47%) who were on continuous entecavir treatment for 10years were calculated. The median age was 50years and follow-up period was 5.5years, with 999, 804, 591, 390, 182 and 87 patients followed up for at least 1, 3, 5, 7, 9 and 10years, respectively. Incremental increases were noted in the rates of undetectable HBV-DNA, ALT normalization, HBeAg seroclearance, and HBsAg seroclearance, reaching 96, 79, 38 and 3.7%, respectively, by the tenth year. The mean decline in HBsAg level from baseline was - 0.08logIU/mL/year. Multivariate analysis identified HBsAg level and genotype (A) as independent predictors of HBsAg seroclearance. Sixteen patients experienced viral breakthrough. The cumulative percentages of patients with viral breakthrough analyzed by the Kaplan-Meier test were 1.5 and 2.5% at years 5 and 10, respectively. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide analogue-naïve CHB patients was associated with an excellent viral response and a low rate of entecavir-resistant mutations at 10years. Baseline HBsAg levels and genotype were predictors of HBsAg seroclearance during entecavir treatment.

Volumetric evaluation of root resorption on the upper incisors using cone beam computed tomography after 1 year of orthodontic treatment in adult patients with marginal bone loss.

To determine upper incisor root resorption, volume loss, and the relationship between root volume loss and tooth movement after 1 year of orthodontic treatment in patients with marginal bone loss. A total of 30 women (46.3 ± 5.4 years old) with moderate upper incisor bone loss who required intrusion during orthodontic treatment were recruited. Pre- and post-treatment cone beam computed tomography images were reconstructed. Upper incisors at pre- and post-treatment were superimposed; labio- and palato-apical, middle, and coronal third root volumes were assessed. Tooth movement and alveolar bone height were measured from lateral cephalometric radiographs and cone beam computed tomography. Changes in root volume/alveolar bone height were compared using paired-sample t-tests, percentage root volume loss for each tooth/segment was evaluated by one-way analysis of variance, and the relationship between percentage root loss and degree of tooth movement was assessed by linear regression. Mean root volume significantly decreased on the labio- and palato-apical aspects of 12 and labio-apical aspects of 21 and 22 ( P ≤ .024). Palato-apical segment volume loss was greater on lateral than central incisors ( P ≤ .016). Two-dimensional root length and cementoenamel junction-bone crest distance did not change between T0 and T1, with no significant relationship between tooth movement amount and percentage root volume loss. Delivery of 40 g intrusive force to the four upper incisors using a T-loop and the leveling phase lead to more apical root volume loss on lateral than central incisors. There was no relationship between extent of tooth movement and upper incisor root volume loss.

Proactively Optimized Infliximab Monotherapy Is as Effective as Combination Therapy in IBD.

Infliximab (IFX) discontinuation is not uncommon during the first year of treatment due to inadequate drug concentrations and anti-IFX antibodies (ATI). Both combination therapy and proactive therapeutic drug monitoring (pTDM) are used to decrease ATI and increase IFX durability. We proposed that monotherapy (Mono) is as effective as combination therapy (Combo) if the first maintenance infusion is dosed based on week 10 pTDM. In a retrospective cohort of 83 patients with inflammatory bowel disease (IBD), we examined the frequency of IFX discontinuation, ATI, infusion reactions, and IFX concentrations during the first year of treatment in patients receiving week 10 pTDM-guided IFX monotherapy (Mono pTDM; n = 16) compared with patients on mono (n = 32) or combination therapy (n = 35) in whom TDM was introduced at or after week 14, per standard of care (SOC). The frequency of IFX discontinuation was lower with Mono pTDM compared with Mono SOC (P = 0.04) but did not differ with Combo SOC (P = 1). At first TDM, no patient in the pTDM strategy had ATI, vs 41% in Mono SOC (P = 0.002) and 6% in Combo SOC (P = 1). Of the 13 subjects with ATI in Mono SOC, 7 (47%) had ATI already at week 14. IFX trough concentrations with Mono pTDM were higher during maintenance compared with Mono SOC (9.5 vs 6.4 µg/mL, P = 0.04) but not Combo SOC. Infliximab durability did not differ between patients on IFX monotherapy dosed based on p-TDM and patients receiving combination therapy. In the absence of concomitant immunosuppression, proactive TDM may improve IFX durability by maintaining higher IFX concentrations entering into maintenance. Further studies are needed to confirm our findings.

PSS14 - Cost Per Responder Analysis of Guselkumab Versus Etanercept Using Efficacy Results from Pivotal Clinical Trials in Patients with Moderate to Severe Plaque Psoriasis

To estimate the cost per responder in the United States (US) for guselkumab relative to etanercept in the induction year of treatment for patients with moderate to severe plaque psoriasis. Psoriasis Area Severity Index (PASI) 90 response rates from two pivotal clinical trials were used. Effectiveness assumptions for the induction year were based on 24 week data for guselkumab from VOYAGE 1 and 24 week data for etanercept from Leonardi et al., 2003 (high dose arm). Response rates were assumed to be unchanged from week 24 through week 52 for both drugs. Dosing was based on the FDA label in the induction year for a 52-week year (guselkumab 8 doses, etanercept 64 doses). It was assumed that patients take every dose as prescribed; costs were based on US wholesale acquisition cost (WAC) as of December 2017. The cost per additional responder for each product was calculated as the cost per induction year divided by the PASI 90 response rate. The PASI 90 response rate at 24 weeks were 80.2% for guselkumab and 30.0% for etanercept respectively. The annual costs for the induction year were $77,472 for guselkumab and $71,072 for etanercept. The cost per additional patient achieving PASI 90 response in the induction year was $96,598.50 for guselkumab versus $236,906.67 for etanercept. This cost per responder analysis demonstrates that guselkumab has a lower cost per PASI 90 responder than etanercept in the induction year and is therefore more cost-effective in patients with moderate to severe plaque psoriasis.

Chronic vagus nerve stimulation reverses heart rhythm complexity in patients with drug-resistant epilepsy: An assessment with multiscale entropy analysis

ObjectiveVagus nerve stimulation (VNS) is an adjunctive treatment in drug-resistant epilepsy. The alterations in heart rate dynamics through VNS are not well understood. This study aimed to determine changes in heart rhythm complexity in association with VNS and to relate the findings to the outcome of VNS treatment in patients with drug-resistant epilepsy. MethodsWe prospectively analyzed 32 patients with drug-resistant epilepsy, who underwent VNS implantation, and 32 age- and sex-matched healthy control subjects. The interictal heartbeat intervals were analyzed using the heart rhythm complexity with multiscale entropy (MSE) and traditional heart rate variability (HRV) analyses based on ambulatory 24-hour electrocardiograms (ECGs). ResultsPatients had significantly decreased complexity indices (Slope 5, Area 1–5, Area 6–15, Area 6–20) on MSE analysis and decreased HRV measurements (standard deviation of the heartbeat interval (SDNN), square root of the mean of sum of squares of the differences between adjacent RR intervals (RMSSD), pNN50, very low frequency (VLF), low frequency (LF), high frequency (HF), total power (TP)) in time and frequency domain analyses. After one year of VNS treatment in patients with drug-resistant epilepsy, there was a trend in an elevated MSE profile with significant higher values between the scales 1 and 9. Vagus nerve stimulation induces a more significant increase of MSE in VNS responders than those in the nonresponders. The conventional HRV measurements did not change. ConclusionOur results suggest that heart rhythm complexity is impaired in patients with drug-resistant epilepsy, and this is at least partially reversed by VNS treatment. Furthermore, VNS-induced effects on heart rate complexity may be associated with the therapeutic response to VNS in patients with drug-resistant epilepsy.

Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease.

To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease. After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute "off" time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments. One year of treatment with opicapone reduced "off" time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in "off" time (-64.9, -39.3, -27.5, and -23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration. Long-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study. This study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) of opicapone is well tolerated and reduces "off" time.

42.2 INFLAMMATION AND GUT MICROBIOME IN FIRST-EPISODE PSYCHOSIS

BackgroundPatients with first-onset psychosis have evidence of impaired glucose tolerance, but otherwise are metabolically healthy when traditional cardiovascular risk markers are used. After antipsychotic treatment is started, there is rapid weight gain and emergence of dyslipidemias. Weight gain and development of abdominal obesity is accompanied by worsening chronic low-grade inflammation. Activation of innate immunity is often present at the onset of disease. One unexplored mechanism possibly contributing to these problems is altered gut microbiota.MethodsThe Helsinki Early Psychosis Study recruited 97 patients with first-episode psychosis and 62 controls into a longitudinal study. Here, data on longitudinal changes in inflammation, weight gain and abdominal obesity during the first year of treatment in patients with first-episode psychosis is presented and compared with matched healthy controls. Three time points (baseline, 2 months, 12 months) are available for patients and two (baseline, 12 month) for controls. The possible contribution of different antipsychotics will be explored, and whether patients who were no longer using antipsychotics at the one-year follow-up have less problems in these measures. First results regarding the gut microbiome will be presented (Schwarz et al. 2017), and the possible contribution of gut microbiota to inflammation and weight gain in first-episode psychosis explored.ResultsOur previous findings from a subset of the study sample found most marked changes in innate immunity chemokines (Mäntylä et al. 2015), whereas full longitudinal data on 38 cyto- and chemokines will be available at the SIRS congress. As a preliminary result on the longitudinal course of inflammation, high-sensitivity C-reactive protein showed a significant increase during the first year of treatment in patients (median baseline 0.65 mg/l, 2 months 0.79 mg/l and 12 months 1.68 mg/l). Data on PBMC gene expression will also be presented, revealing notable differences related to different antipsychotic use.DiscussionThe findings will be discussed in the context of to what extent they may reflect underlying disease mechanisms and environmental contributions, including gut microbiota alterations, and to what extent inflammation is a secondary phenomenon related to antipsychotic use and weight gain.References1) Mäntylä T, Mantere O, Raij TT, Kieseppä T, Laitinen H, Leiviskä J, Torniainen M, Tuominen L, Vaarala O, Suvisaari J. Altered activation of innate immunity associates with white matter volume and diffusion in first-episode psychosis. PLoS One. 2015 May 13;10(5):e0125112.2)Schwarz E, Maukonen J, Hyytiäinen T, Kieseppä T, Orešič M, Sabunciyan S, Mantere O, Saarela M, Yolken R, Suvisaari J. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr Res. 2017 [Epub ahead of print]

Long-term efficacy and predictors of remission following adalimumab treatment in peripheral spondyloarthritis: 3-year results from ABILITY-2

ObjectivesDescribe efficacy and safety of 3 years of adalimumab treatment in patients with peripheral spondyloarthritis (pSpA) and identify predictors of remission.MethodsPatients with pSpA were randomised to adalimumab 40 mg every...

Patients with Crohn's Disease with High Body Mass Index Present More Frequent and Rapid Loss of Response to Infliximab.

Infliximab (IFX) is effective in inducing and maintaining remission in patients with luminal and anoperineal Crohn's disease (CD). However, treatment failure within 12 months after initiating IFX is observed in a significant proportion of patients. The aim of the present study was to determine whether the body mass index (BMI) affects response to IFX during the first year of treatment in patients with CD. All patients with luminal CD who began IFX between January 2010 and May 2014 were prospectively included. BMI was calculated before IFX treatment was begun, and patients were divided into 3 groups: normal BMI (BMI < 25 kg/m), overweight patients (BMI of 25.0-30 kg/m), and obese patients (BMI > 30.0 kg/m). The primary outcome was to evaluate the rate and delay of IFX optimization during the first year of treatment among normal weight, overweight, and obese patients. One hundred forty patients were included. Demographic and clinical characteristics at IFX initiation were comparable among the 3 groups. Within 12 months after the initiation of IFX, the rate of IFX optimization was significantly higher in overweight and obese patients than in the normal BMI group: 52%, 56%, and 20%, respectively (P = 0.0002). The median time until optimization of IFX was significantly shorter in overweight and obese patients than in the normal BMI group: 7, 7, and 10 months, respectively (P = 0.03). A BMI >25 kg/m was significantly associated with IFX optimization within 12 months on multivariate analysis. This is the first study to show that optimization of IFX is more frequent and faster in obese and overweight patients with CD and occurs within 12 months after beginning IFX, suggesting that an induction regimen with higher doses of IFX and a tight control of IFX concentrations may be needed in these patients.

Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.

To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

The effect of certolizumab pegol on skin manifestations of psoriatic arthritis over 4 years of treatment in patients with and without prior anti-TNF exposure

The effect of certolizumab pegol on skin manifestations of psoriatic arthritis over 4 years of treatment in patients with and without prior anti-TNF exposure

337 Long-term clinical outcomes after 2 years of Ixekizumab treatment in patients with moderate-to-severe psoriasis with a focus on absolute PASI

337 Long-term clinical outcomes after 2 years of Ixekizumab treatment in patients with moderate-to-severe psoriasis with a focus on absolute PASI

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years...

NaoXinTong Enhances Atorvastatin-induced Plaque Stability While Ameliorating Atorvastatin-induced Hepatic Inflammation.

Buchang NaoXinTong (NXT) is a Chinese medicine that has been used for many years for treatment of patients with coronary heart disease (CHD) in China. Statins substantially reduce hypercholesterolemia and CHD mortality and morbidity. However, there is still a lot of CHD patients who do not respond well to statin therapy. Herein, we report the effects of NXT on atorvastatin-inhibited atherosclerosis and atorvastatin-induced hepatic side effects. After 10 weeks of high-fat diet (HFD) feeding, apoE-deficient mice were randomly divided into 4 groups and received the following treatment for another 8 weeks: group 1, HFD; group 2, HFD containing NXT; group 3, HFD containing atorvastatin; and group 4, HFD containing both NXT and atorvastatin. After treatment, serum lipid profiles, atherosclerotic lesions, and hepatic lipid content and inflammation were determined. NXT moderately increased high-density lipoprotein cholesterol levels, although had little effect on atorvastatin-induced reduction of low-density lipoprotein cholesterol levels. Both NXT and atorvastatin reduced en face lesions and sinus lesions of aortic root. In addition, NXT enhanced atorvastatin-induced lesion plaque stability by increasing smooth muscle cell/collagen content and reducing macrophage accumulation and calcification in lesion areas. The co-treatment of NXT and atorvastatin further reduced hepatic triglyceride levels by downregulating acyl-CoA:diacylglycerol acyltransferase 1 while activating hormone-sensitive lipase, adipose triglyceride lipase, and comparative gene identification-58 expression. The AMPKα pathway was also further activated by the co-treatment. More importantly, the liver injuries caused by atorvastatin, such as hepatic inflammation and elevated serum aminotransferase activities, were substantially attenuated by NXT. Therefore, our study demonstrates that NXT enhances atorvastatin-induced plaque stability and ameliorates atorvastatin-induced hepatic side effects.